Regulatory effect of nanoparticles on Endoplasmic Reticulum (ER)
The endoplasmic reticulum is a cellular compartment involved in protein folding and maturation (Zid et al.). It is particularly involved in the suppression of protein aggregation through multiple levels by maintaining the accuracy of accurate transcription of DNA to RNA and then the translation of RNA to proteins as well as chaperons of nascent and unfolded proteins (Ellgaard, Molinari, & Helenius, 1999).
The main limiting stage in the biogenesis of both transmembrane or secretory proteins is the folding process in the ER. The chaperones and folding enzymes are responsible for different stages of quality control and protein folding processes (Naidoo & Brown, 2012). The reduced efficacy of chaperones and foldases by aging lead to the cumulation of abnormal proteins in the ER and finally trigger the activation of unfolded protein response, which is related to ER-stress (Berridge, 2002). This triggers some of the protective cellular responses, including the up-regulation of some chaperones to promote the restoration of protein structures, proteolysis of misfolded proteins, and attenuation of protein translation (Brown & Naidoo, 2010).
By increasing the age, the potency of processing the abnormal proteins decreases following the diminished components of the ER stress and UPR tools. This inefficient protein refolding process leads to age-associated disorders, such as neurodegenerative deteriorations, vascular inflammation, atherosclerosis, and a variety of cancer diseases (Forman, Lee, & Trojanowski, 2003; Johnson et al., 2008).
Drugs or nanomaterials can alleviate the ER stress through improving the accurate folding of proteins, modulating the efficiency of ER-related degradation, and increasing the recognition of misfolded proteins that may lead to the prevention of age-related diseases and disorders (Naidoo & Brown, 2012). There has been no report of nanoparticle stress inhibition in the ER with the aim of delaying or treating aging. Therefore, it can be considered as a new research target for this purpose.